The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo

© 2008 Hutt et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Developmental Biology 8 (2008): 1, doi:10.1186/1471-213X-8-1.Environmental toxicants, whose actions are often mediated through the aryl hydrocarbon receptor (AhR) pathway, pose risks to the health and well-being of exposed species, including humans. Of particular concern are exposures during the earliest stages of development that while failing to abrogate embryogenesis, may have long term effects on newborns or adults. The purpose of this study was to evaluate the effect of maternal exposure to the AhR-specific ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat pre-implantation embryos with respect to nuclear and cytoskeletal architecture and cell lineage allocation. We performed a systematic 3 dimensional (3D) confocal microscopy analysis of rat pre-implantation embryos following maternal exposure to environmentally relevant doses of TCDD. Both chronic (50 ng/kg/wk for 3 months) and acute (50 ng/kg and 1 μg/kg at proestrus) maternal TCDD exposure disrupted morphogenesis at the compaction stage (8–16 cell), with defects including monopolar spindle formation, f-actin capping and fragmentation due to aberrant cytokinesis. Additionally, the size, shape and position of nuclei were modified in compaction stage pre-implantation embryos collected from treated animals. Notably, maternal TCDD exposure did not compromise survival to blastocyst, which with the exception of nuclear shape, were morphologically similar to control blastocysts. We have identified the compaction stage of pre-implantation embryogenesis as critically sensitive to the effects of TCDD, while survival to the blastocyst stage is not compromised. To the best of our knowledge this is the first in vivo study to demonstrate a critical window of pre-implantation mammalian development that is vulnerable to disruption by an AhR ligand at environmentally relevant doses.This research was supported by NIH/NIEHS-012916 (BKP), ESHE Fund (DFA), Hall Family Foundation (DFA and KJH) and Biomedical Research Training Grant KUMC (KJH)

Electro-elastic tuning of single particles in individual self-assembled quantum dots

We investigate the effect of uniaxial stress on InGaAs quantum dots in a charge tunable device. Using Coulomb blockade and photoluminescence, we observe that significant tuning of single particle energies (~ -0.5 meV/MPa) leads to variable tuning of exciton energies (+18 to -0.9 micro-eV/MPa) under tensile stress. Modest tuning of the permanent dipole, Coulomb interaction and fine-structure splitting energies is also measured. We exploit the variable exciton response to tune multiple quantum dots on the same chip into resonance.Comment: 16 pages, 4 figures, 1 table. Final versio

Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women

Associational studies suggest higher intakes/blood levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) are associated with reduced breast cancer risk. We performed a pilot study of high-dose EPA + DHA in postmenopausal women to assess feasibility before initiating a phase IIB prevention trial. Postmenopausal women with cytologic evidence of hyperplasia in their baseline random periareolar fine needle aspiration (RPFNA) took 1,860 mg EPA +1500 mg DHA ethyl esters daily for 6 months. Blood and breast tissue were sampled at baseline and study conclusion for exploratory biomarker assessment, wit

The Environmental Toxicant 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Disturbs the Establishment and Maintenance of Cell Polarity in Preimplantation Rat Embryos1

Maternal exposure to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a variety of defects in compaction-stage embryos, including monopolar spindle formation, errors in chromosome segregation, and fragmentation resulting from aberrant cytokinesis. In this study, we investigated the possibility that a failure in centrosome duplication, separation, or positioning within blastomeres might underlie the observed effects of TCDD on early embryos. The subcellular localization of the centrosomal marker TUBG1 was analyzed in preimplantation embryos collected from female rats exposed to either chronic (50 ng kg−1 wk−1 for 3 wk) or acute (50 ng/kg or 1 μg/kg at proestrus) doses of TCDD. In treated embryos, interphase TUBG1 foci were more abundant and cortically displaced when compared to those in controls. At prophase, some blastomeres exhibited a single large perinuclear TUBG1 aggregate, suggesting a failure in centrosome duplication or separation. Furthermore, the presence of monopolar spindles at metaphase was confirmed by the localization of TUBG1 to the single spindle pole. Therefore, the misregulation of centrosome number and localization, as indicated by TUBG1 staining, may contribute to errors in chromosome segregation and cytokinesis in embryos following maternal TCDD exposure

The environmental toxicant 2,3,7,8-tetrachlorodibenzo--dioxin disrupts morphogenesis of the rat pre-implantation embryo-6

<p><b>Copyright information:</b></p><p>Taken from "The environmental toxicant 2,3,7,8-tetrachlorodibenzo--dioxin disrupts morphogenesis of the rat pre-implantation embryo"</p><p>http://www.biomedcentral.com/1471-213X/8/1</p><p>BMC Developmental Biology 2008;8():1-1.</p><p>Published online 2 Jan 2008</p><p>PMCID:PMC2254588.</p><p></p>ssed for visualization of microtubules, f-actin and DNA by confocal microscopy. (A-D) Control 8-cell pre-implantation embryo with blastomeres of similar size and shape, basally positioned interphase nuclei and cytoplasmic microtubule arrays. F-actin is distributed at the cell cortex. (E-H) Control 12-cell pre-implantation embryo with a normal bipolar mitotic spindle (E and H, arrows), metaphase chromosome configuration (F, arrow) and cortical f-actin localization (G, arrow). (I-L) 50 ng/kg/wk TCDD exposed 9-cell pre-implantation embryo with abnormal mitotic spindles (L, arrow) and metaphase chromosome configurations (J, arrow), and enhanced f-actin cortical localization (K, arrow) in multiple blastomeres. (M-P) 50 ng/kg/wk TCDD exposed 8-cell pre-implantation embryo with an anucleate fragment (M, arrow) and abnormal cytokinesis (O, arrows). Monopolar spindle (P, arrow). PB, polar body. Scale bar: 15 μm

The environmental toxicant 2,3,7,8-tetrachlorodibenzo--dioxin disrupts morphogenesis of the rat pre-implantation embryo-7

<p><b>Copyright information:</b></p><p>Taken from "The environmental toxicant 2,3,7,8-tetrachlorodibenzo--dioxin disrupts morphogenesis of the rat pre-implantation embryo"</p><p>http://www.biomedcentral.com/1471-213X/8/1</p><p>BMC Developmental Biology 2008;8():1-1.</p><p>Published online 2 Jan 2008</p><p>PMCID:PMC2254588.</p><p></p>fferent pre-implantation embryo) for each group (Control and 50 ng/kg/wk TCDD) were compared